dihydropyridines and Granuloma

1. To determine biological functions of platelet-activating factor (PAF) in chronic inflammation, we have investigated the kinetics of angiogenesis, inflammatory cells recruitment and cytokine production in sponge-induced granuloma in wild type and PAF receptor-deficient mice (PAFR-KO). 2. Angiogenesis as determined by morphometric analysis and hemoglobin content was significantly higher in the implants of PAFR-KO mice at all time points. Treatment with PAF receptor antagonist UK74505 (30 mg kg(-1)) also increased angiogenesis in sponge implants. 3. Neutrophils and macrophages accumulation, as determined by myeloperoxidase and N-acetylglucosaminidase activities in the supernatant of implanted sponges were markedly decreased in PAFR-KO mice. Surprisingly, the levels of the proinflammatory chemokines, keratinocyte-derived chemokine and chemokine monocyte chemoattractant protein 1 were higher in the implants of the transgenic animals. 4. We have shown that angiogenesis was stimulated in PAFR-KO mice whereas inflammation was decreased, indicating that PAF is an endogenous regulator of new blood vessels formation in the inflammatory microenvironment induced by the sponge implant.

Topics: Acetylglucosaminidase; Administration, Topical; Animals; Blood Vessels; Chemokines; Dihydropyridines; Fibroblasts; Granulation Tissue; Granuloma; Hemoglobins; Imidazoles; Implants, Experimental; Inflammation; Macrophages; Mice; Mice, Inbred BALB C; Mice, Knockout; Neovascularization, Pathologic; Neutrophils; Peroxidase; Platelet Activating Factor; Platelet Membrane Glycoproteins; Polyurethanes; Porifera; Receptors, G-Protein-Coupled; Skin