Bio medical report

In the blood, two types of white blood cells, neutrophil leukocytes, and monocytes are phagocytic. Neutrophils are small, granular leukocytes that quickly appear at the site of a wound and ingest bacteria. Monocytes are larger, with a large, kidney-shaped nucleus; they appear about three days after infection and scavenge for bacteria, foreign particles, dead cellular material, and protozoa. Most phagocytic activity takes place outside the vascular system, among the cells. For example, foreign material in the lymph system is phagocytized by fixed cells in the lymph nodes; similarly, the vascular system is cleansed by fixed cells in the spleen, liver, and bone marrow that engulf aged red blood cells and foreign bodies. To determine whether zymosan, PMA, and BIM are recognized by CR3 through distinct sugars, competition experiments were performed with single mono- or polysaccharides.

The clear inhibition of zymosan ingestion obtained by combining β-glucan and mannan suggested that internalization of this particle might involve two subsites of CR3 specific for glucose and mannose moieties, respectively (Kim, Wonki, et al. In contrast, this sugar combination did not produce a significant inhibitory effect on PMA and BIM phagocytosis, in line with the previous observation that zymosan and mannan minimally inhibited the adherence of nonopsonized to CR3 transfected CHO cells It is possible that ingestion of mycobacteria by CR3 either involves different molecules or more complex saccharides than ingestion of zymosan or is highly sensitive to the sugar environment on the bacteria. Indeed, antigen 85C, present on the surfaces of mycobacteria, illustrates the promotion to the binding of microbeads coated with mycobacterial products to CR3 (Kanehiro, Yuichi, et al.

, 2018) In the same way, the affinity of the mannose receptor is significantly increased when mannose moieties are contained in PMA. Only combinations of pairs of three of these, which recognized epitopes restricted to the N-terminal part of CD11b, efficiently blocked phagocytosis (Sumagin, Ronen, et al. The patterns of antibody inhibition of M. tuberculosis ]and differ to some extent. This could be explained by differences between the strains used because even in a single strain, differences have been reported: of two substrains of H37Rv, one binds to CR3 and the other does not and, depending on the physiological state of M. avium, it can or cannot be ingested through CR3. from the results, it has been demonstrated that such interactions may generate conformational changes of the I domain recognized by 2LPM MAbs.

Such accessory receptors may be different in CHO cells, explaining the smaller inhibitory effect of 2LPM MAbs on zymosan phagocytosis compared to that observed in U937 cells. Finally, using U937 cells, we also showed that CR3-mediated phagocytosis of zymosan-induced O2− production. The observation that CR3 can initiate distinct cell responses depending on the binding site recognized by particles correlates with previous data obtained with neutrophils. In these cells, which also express CR3 but not the mannose receptor, unopsonized zymosan stimulates O2− production whereas it fails to do so when particles are iC3b coated We demonstrated that ] zymosan use the same receptor, but its coincubation is not affected by the production of O2− triggered by zymosan, probably because the number of receptors at the cell surface is not limiting (Potter, Timothy M.

In addition to CR3, mycobacteria have been shown to enter monophonically into macrophages through several receptors, but their relative participation in vivo infections is difficult to establish (Sukegawa, Sayaka, et al 2018). In CD18-deficient mice, a comparable level of tissue infection by zymosan has been displayed, suggesting too that when a phagocytic receptor is lacking, mycobacteria use another one. It is therefore difficult to conclude from these experiments whether CR3 is involved in primary mycobacterial infection in human lungs (Mpongoshe, Vuyiseka. 2014) To determine the receptor hierarchy in nonopsonic phagocytosis of mycobacteria, experiments on both human macrophages and cells transfected with one or combinations of phagocytic receptors should be performed. This would shed light on invasion strategies of pathogens and help to determine whether the mode of binding and the route of entry play roles in the subsequent bactericidal responses and the fate of mycobacteria.