New insights in chemokine interaction

• Published in: International journal of immunopathology and pharmacology 1994, Vol.7 (3), p.221-225
• Main Authors: Bertini, R, Bizzarri, C, D'Ettorre, C, Bertolasi, G, Ruggiero, P, Tagliabue, A, Boraschi, D
• Format: Article
• Language: English
• ISSN: 0394-6320

Recruitment of leukocytes from the blood compartment into tissues is a crucial process in inflammatory reactions and immunity, which involves complex interactions of leukocytes with vascular endothelium and requires secretion of chemotactic factors. Recently, a new superfamily of low molecular weight (8-10 kDa) chemotactic proteins active on different leukocyte populations has been identified. The structural hallmark of these mediators, named chemokines, is represented by four highly conserved cysteine (Cys) residues. According to the position of the first two Cys, two subfamilies of chemokines have been defined: chemokines alpha (Cys-X-Cys) and chemokines beta (Cys-Cys), which share an aminoacid homology of about 20-40%. Chemokines alpha include interleukin-8 (IL-8), melanocyte growth-stimulating factor (MGSA/GRO), platelet factor 4 (PF4), neutrophil activating protein 2 (NAP-2) and epithelial neutrophil-activating protein (ENA-78). IL-8, the best characterized chemokine alpha , is a chemotactic and activating factor for human neutrophils (PMN) as well as for T lymphocytes and basophils. Chemokines beta , which include monocyte chemotactic protein -1 (MCP-1), MCP-2, MCP-3, LD78/MIP-1 alpha , RANTES, Act2 and I-309, are chemotactic for human monocytes, basophils, T lymphocytes and eosinophils, and could also activate some functions of monocytes, basophils and eosinophils. In vivo, subcutaneous injection of MCP-1, MCP-2 or MCP-3 into rabbit skin induces monocytic infiltration. Some chemokines beta also possess hematopoiesis regulatory activity. In fact, LD78, MCP-1 and RANTES have been shown to inhibit hematopoietic stem cell and myeloid progenitor cell proliferation in vivo and in vitro. Thus, chemokines beta can be used as myeloprotective agents against the toxic effect of myelosuppressive chemotherapy. Chemokines are produced by many cell types (monocytes, T lymphocytes, fibroblasts, endothelial cells, keratinocytes, chondrocytes, smooth muscle cells and several tumor cell lines), generally in response to inflammation-related stimuli. Indeed, inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) and exogenous agents such as bacterial products, viruses and injurious agents (silica or Na urate crystals) have been shown to stimulate the production of chemokines, indicating the crucial role of these proteins in inflammatory diseases as well as in several autoimmune pathologies. In fact, during degenerative and inflammatory arthr