Moreover, SAP antigens were localized selleck chem inhibitor to the seminiferous tubules containing late spermatids by immunohistochemistry, and epididy mal sperm and epithelial cells were also strongly positive for SAP, suggesting that at least some SAP antigen associates with the sperm membrane during the later stages of spermatogenesis and or the epididymal maturation process. The results from the experiments in which sperm were treated with EDTA Inhibitors,Modulators,Libraries indicate that most SAP mole cules are attached to the human sperm membrane in a calcium independent manner. SAP can bind to glycosaminoglycans and amyloid proteins in a cal cium independent manner, and it associates with microbial polysaccharides Inhibitors,Modulators,Libraries and extracellular matrix com ponents through carbohydrate determinants, including heparin and 6 phosphorylated mannose.
However, whether SAPs membrane attachment involves carbohy drate structures on the sperm surface, or occurs through interaction with other molecules situated in the outer leaflet Inhibitors,Modulators,Libraries of the sperm plasma membrane, remains to be determined. SAP can activate the classical complement pathway via interaction with C1q, and complement components on the head of acrosome reacted sperm Inhibitors,Modulators,Libraries have been sug gested to facilitate sperm egg binding via complement receptors on the egg surface. However, SAP is an unlikely participant in such interactions as it mainly localizes to the neck and tail regions of intact, washed human sperm, and IF staining of permeabilized sperm failed to detect SAP antigens in the acrosome compart ment.
Recent studies suggest that SAP can act as an opsonin, facilitating the uptake of apoptotic cells by direct interaction with the Fcg receptors on macro phages. Binding of SAP and other members of the innate immune system to the asymmetric pattern of phospholipids found on apoptotic cells is also thought to have important immuno modulatory effects on the ingesting phagocytes, Inhibitors,Modulators,Libraries triggering them to release anti inflammatory cytokines rather than to produce inflammatory cytokines, thereby collaborating T cell suppression and the maintenance of tolerance. SAP binding and stabilization of cellular debris and soluble immune complexes thus appear to facilitate their subsequent clearance by phagocytes. In addition, SAP binds DNA and chromatin with high affi nity and avidity, and it has been proposed that SAPs fairly chaperone like binding and stabilization of nuclear macromolecule antigens protect them from pro teolysis and prevent subsequent spread of immunogenic degradation products.