Target type: biologicalprocess
The process of regulating the proliferation and elimination of macrophage cells such that the total number of myeloid cells within a whole or part of an organism is stable over time in the absence of an outside stimulus. [GOC:dph, PMID:21727904]
Macrophage homeostasis is a tightly regulated process that ensures the appropriate number and function of macrophages in tissues. It involves a complex interplay of factors, including:
**1. Macrophage Development and Differentiation:**
* **Hematopoietic Stem Cells (HSCs):** Macrophages originate from HSCs in the bone marrow. HSCs differentiate into monocyte precursors.
* **Monocytes:** Monocytes are circulating blood cells that differentiate into macrophages in tissues.
* **Tissue-Specific Differentiation:** Once in tissues, monocytes differentiate into specialized macrophages with unique functions based on their location and the local microenvironment.
**2. Macrophage Survival and Proliferation:**
* **Growth Factors and Cytokines:** Macrophages respond to various growth factors and cytokines, including colony-stimulating factors (CSFs) and macrophage colony-stimulating factor (M-CSF), which promote their survival and proliferation.
* **Apoptosis:** Macrophages undergo programmed cell death (apoptosis) as part of normal homeostasis or in response to stress or damage.
**3. Macrophage Activation and Function:**
* **Immune Responses:** Macrophages are key players in innate immunity, engulfing and destroying pathogens, presenting antigens to T cells, and producing cytokines that activate other immune cells.
* **Tissue Repair and Regeneration:** Macrophages contribute to tissue repair and regeneration by clearing debris, promoting angiogenesis, and secreting growth factors.
* **Phagocytosis:** Macrophages are professional phagocytes, engulfing and destroying pathogens, cellular debris, and other foreign materials.
**4. Macrophage Migration and Trafficking:**
* **Chemotaxis:** Macrophages migrate to sites of inflammation or injury in response to chemotactic signals, such as chemokines.
* **Tissue-Specific Localization:** Macrophages reside in specific tissues and organs, where they perform specialized functions.
**5. Macrophage Polarization:**
* **M1 (Classically Activated) Macrophages:** These macrophages are activated by Th1 cytokines (IFN-gamma, TNF-alpha) and promote inflammatory responses, killing pathogens, and tissue damage.
* **M2 (Alternatively Activated) Macrophages:** These macrophages are activated by Th2 cytokines (IL-4, IL-10) and promote tissue repair, angiogenesis, and anti-inflammatory responses.
**6. Macrophage Homeostatic Mechanisms:**
* **Negative Feedback Loops:** Macrophages can release factors that suppress their own proliferation or promote apoptosis, maintaining a balance in their numbers.
* **Microenvironmental Cues:** The local microenvironment within tissues influences macrophage differentiation, activation, and survival.
**7. Macrophage Dysregulation and Disease:**
* **Inflammation:** Dysregulation of macrophage homeostasis can contribute to chronic inflammation and autoimmune diseases.
* **Cancer:** Macrophages can play both pro- and anti-tumorigenic roles, depending on the context.
**Overall, macrophage homeostasis is a dynamic and complex process that is crucial for maintaining immune function, tissue integrity, and overall health.**'
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Protein | Definition | Taxonomy |
---|---|---|
Ubiquitin carboxyl-terminal hydrolase BAP1 | A ubiquitin carboxyl-terminal hydrolase BAP1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92560] | Homo sapiens (human) |
Lysosomal acid lipase/cholesteryl ester hydrolase | A lysosomal acid lipase/cholesteryl ester hydrolase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P38571] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
5-(1,3-benzodioxol-5-yl)-N-(2-furanylmethyl)-7-(trifluoromethyl)-2-pyrazolo[1,5-a]pyrimidinecarboxamide | pyrazolopyrimidine | ||
N-[2-(4-acetyl-1-piperazinyl)phenyl]-2-(5-methyl-2-propan-2-ylphenoxy)acetamide | piperazines | ||
lalistat 2 | |||
4-[[2-[(6-methyl-4-oxo-1H-pyrimidin-2-yl)thio]-1-oxoethyl]amino]benzoic acid ethyl ester | amidobenzoic acid |