muramidase and Acquired-Immunodeficiency-Syndrome

Host defense responses of the human female genital tract mucosa to pathogenic microbes and viruses are mediated in part by the release of antimicrobial substances into the overlying mucosal fluid. While host defense has long been considered a prominent function of vaginal and cervical mucosae, evidence that cationic antimicrobial peptides and proteins have fundamental roles in the innate host defense of this tissue has only recently become available. This chapter explores elements of the physical and chemical defense barriers of the cervicovaginal mucosa, which protect against infections of the lower genital tract. Cationic antimicrobial and antiviral polypeptide components of cervicovaginal fluid are discussed in detail, with special emphasis placed on the defensin family of peptides as well as polypeptides that are active against viruses such as HIV-1. The reader should be cognizant that each polypeptide by itself does not provide complete protection of the genital tract. On the contrary, the abundance and multiplicity of antimicrobial peptides and proteins suggest protection of the cervicovaginal mucosa may be best realized from the aggregate effector molecules.

Topics: Acquired Immunodeficiency Syndrome; Antimicrobial Cationic Peptides; Candidiasis, Vulvovaginal; Cathelicidins; Cervix Uteri; Defensins; Female; Histones; Humans; Immunity, Innate; Lactoferrin; Leukocyte L1 Antigen Complex; Muramidase; Proteinase Inhibitory Proteins, Secretory; Proteins; Trichomonas Vaginitis; Vagina; Vaginosis, Bacterial

Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.

Topics: Acquired Immunodeficiency Syndrome; Cell Line; Cell Membrane; Gene Products, gag; HIV Infections; HIV-1; Humans; Jurkat Cells; Microscopy, Electron; Microscopy, Electron, Transmission; Muramidase; Plasmids; RNA Processing, Post-Transcriptional; RNA, Small Interfering; Signal Transduction; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins; Virus Replication

Human immunodeficiency virus (HIV) associated salivary gland disease is defined as the presence of enlargement of one or more major salivary glands and/or diminished salivary function in an HIV infected individual. It has a number of similarities to, as well as differences from, Sjögren's syndrome (SS). We studied the sialochemistry of stimulated parotid saliva of 11 patients with HIV associated salivary gland disease and bilateral parotid gland enlargement, and compared these findings with those of 15 HIV negative controls, 13 HIV positive individuals with no salivary gland involvement and 18 individuals with SS. The patients with HIV associated salivary gland disease had a significant decrease in the level of salivary protein, with increases in salivary IgA, lysozyme and albumin compared to the HIV negative controls. There were no changes in concentration of electrolytes. The sialochemistry among the patients with HIV associated salivary gland disease was unrelated to the degree of immune suppression and did not change over a 6 month period. The observed changes were similar to those of SS but less pronounced. The similar clinical, histologic and sialochemical features of HIV associated salivary gland disease and SS suggest that these conditions share common pathogenetic mechanisms, which may be modified in the former by the HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; Humans; Immunoglobulin A; Male; Middle Aged; Muramidase; Saliva; Salivary Gland Diseases; Salivary Glands; Sjogren's Syndrome

Hyaline globules (HG) were detected in 51 of 54 Kaposi's sarcoma (KS) lesions (94.4%), including all four non-acquired immunodeficiency syndrome (AIDS) cases of cutaneous KS in this group of cases. Thus, there was no correlation between the presence of HG and the presence or absence of AIDS, nor could we demonstrate any relationship between the presence or prominence of HG and either the histologic pattern or anatomical distribution of KS. HG were located mainly in the cytoplasm of perivascular cells, histiocytoid cells, and spindle-shaped cells and occasionally in endothelial cells lining vessels or slit-like spaces. Extracellular HG were also seen. HG stained positively with periodic acid-Schiff with and without diastase digestion and with phosphotungstic acid-hematoxylin. HG were immunohistochemically negative for alpha 1-antitrypsin, alpha 1-antichymotrypsin, lysozyme, and Factor VIII-related antigen, but the cells containing HG were often positive for alpha 1-antichymotrypsin and occasionally for alpha 1-antitrypsin and Factor VIII-related antigen. HG were also detected in five of six angiosarcomas, two of ten pyogenic granulomas, and seven of 32 inflammatory granulation tissues. These were immunohistochemically similar to HG in KS. Thus, HG are not specific for KS. We support the interpretation that HG are most likely digested erythrocytes.

Topics: Acquired Immunodeficiency Syndrome; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Female; Granulation Tissue; Granuloma; Hemangiosarcoma; Humans; Hyalin; Immunohistochemistry; Inclusion Bodies; Male; Muramidase; Sarcoma, Kaposi; von Willebrand Factor

Thirty-seven HIV-1-positive patients contributed salivary samples from individual major salivary glands. Nineteen patients were unmedicated and asymptomatic, and 18 patients had developed signs of AIDS. Salivas from 15 healthy males served as controls. Levels of four salivary antimicrobial proteins (lactoferrin, lysozyme, secretory IgA, and histatins) were determined, as well as total fluid output of the major salivary glands. Concentrations of all four salivary antimicrobial proteins were found to be increased in the stimulated submandibular/sublingual saliva of all HIV-1-positive patients as well as the subset of unmediated HIV-1-positive patients. Those patients with evidence of oral candidiasis had the highest concentrations of lysozyme and histatins, potent antifungal proteins, in their saliva. Although the etiology of these protein increases is still unknown, these results further document salivary changes following HIV-1 infection.

Topics: Acquired Immunodeficiency Syndrome; Adult; HIV Seropositivity; HIV-1; Humans; Immunoglobulin A, Secretory; Lactoferrin; Lactoglobulins; Male; Middle Aged; Muramidase; Proteins; Saliva; Salivary Proteins and Peptides

A pathogenic retrovirus (HTLV-III) has recently been isolated in the seminal plasma (SP) of patients with AIDS. In order to test whether SP may influence non-specific immunity we compared the influence of SP on the phagocytic release of lysozyme, chemotaxis and chemiluminescence. SP inhibited the release of lysozyme from granulocytes in a log-linear fashion; incubation with undiluted SP resulted in about 50% inhibition. Chemotaxis of granulocytes remained stable under the influence of SP. Chemiluminescence of both granulocytes and monocytes was completely blocked by undiluted SP; 1000-fold dilutions still caused an inhibition of about 20%. The separation of SP by column chromatography yielded fractions with a molecular weight of 10(4) to 2 X 10(4), 10(5) to 4 X 10(5) and greater than 10(6) inhibiting chemiluminescence. A cell-free chemiluminescent system showed the reduction of chemiluminescence to be based to a large extent on quenching of the photons generated. Our results indicate that SP possesses potent properties that suppress non-specific immunity, possibly an important predisposing factor to AIDS.

Topics: Acquired Immunodeficiency Syndrome; Chemotaxis, Leukocyte; Granulocytes; Humans; Immune Tolerance; Leukocytes; Luminescent Measurements; Male; Muramidase; Phagocytes; Phagocytosis; Semen

It was shown recently that monocytoid cells express B-cell-restricted antigens and polyclonal surface immunoglobulins, and the term monocytoid B lymphocytes (MBL) has thus been offered as a more appropriate designation. Although most commonly seen in toxoplasmic lymphadenitis, MBL have been observed in a variety of reactive and neoplastic conditions involving lymph nodes. In the present study MBL were found in 17 of 22 lymph nodes from 20 patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy. In all 17 samples, the MBL were found in lymph nodes with florid reactive follicular hyperplasia, and they were geographically close to the hyperplastic lymphoid follicles. However, MBL were not detected in lymph nodes showing involuted follicles or lymphocyte depletion. The disappearance of MBL apparently parallels the progressive involution of secondary follicles. Leu-3+/Leu-2+ (T-helper/T-suppressor) ratios were studied in 14 lymph node cell suspension samples and ten peripheral blood samples. The lymph node Leu-3+/Leu-2+ ratios were significantly lower in AIDS-related lymphadenopathy than in non-AIDS-related reactive follicular hyperplasia (P less than 0.001); the peripheral blood ratios were decreased in nine of the ten cases. The diminished T-helper status in patients with AIDS and AIDS-related lymphadenopathy may be relevant to the immunopathogenesis of follicular involution and, indirectly, to the disappearance of MBL.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Adult; Antigens, Differentiation, B-Lymphocyte; Antigens, Surface; B-Lymphocytes; Humans; Leukocyte Count; Lymph Nodes; Lymphatic Diseases; Male; Middle Aged; Muramidase; Receptors, Antigen, B-Cell; T-Lymphocytes

Comparison of idiopathic Kaposi's sarcoma in Europe and Africa and Kaposi's sarcoma in connection with AIDS shows an identical morphological appearance in all three types. Ultrastructural and immunohistological investigations indicate that the tumour originates from the endothelial cells of proliferating capillaries and is therefore a vascular tumour. The clinical course and the sites of manifestation differ slightly in idiopathic cases and those occurring in connection with AIDS. This effect may be determined by the general condition of the patient, the state of immune deficiency and the influence of opportunistic infections.

Topics: Acquired Immunodeficiency Syndrome; Africa; Capillaries; Europe; Factor VIII; Humans; Intermediate Filament Proteins; Lymph Nodes; Muramidase; S100 Proteins; Sarcoma, Kaposi; Skin

beta 2-Microglobulin (beta 2-M) levels in sera and urines, and lysozyme levels in sera, were quantitated in healthy heterosexual men and several groups of homosexual males. The mean beta 2-M levels in sera and urines and lysozyme levels in sera of healthy heterosexual and homosexual men were not significantly different. However, beta 2-M levels in patients with lymphadenopathy syndrome and AIDS were elevated. The mean beta 2-M level in sera of 11 patients with the lymphadenopathy syndrome was 4016 +/- 473 micrograms/l (SEM) (P less than 0.001) and 5409 +/- 462 micrograms/l (P less than 0.001) in 27 patients with AIDS. Similarly, beta 2-M levels in the urines of patients with chronic diarrheal syndrome, lymphadenopathy syndrome, and those meeting the CDC surveillance definition of AIDS were also significantly elevated (P less than 0.025). The mean lysozyme levels in the sera of 11 patients with the lymphadenopathy syndrome was 16.58 +/- 0.04 microgram/ml, and in 27 patients with AIDS 15.40 +/- 1.16 microgram/ml, compared to the mean level obtained in normal heterosexual men of 6.67 +/- 0.42 microgram/ml (P less than 0.001). The results of this study suggest that measuring beta 2-M in serum and urine and lysozyme levels in serum might provide additional useful parameters for the evaluation of patients with AIDS and prodromal syndromes.

Topics: Acquired Immunodeficiency Syndrome; Antibodies, Monoclonal; beta 2-Microglobulin; Creatinine; Humans; Leukocyte Count; Lymphocytes; Male; Muramidase; T-Lymphocytes