The opsonizing ligand on Salmonella typhimurium influences incorporation of specific, but not azurophil, granule constituents into neutrophil phagosomes.

Abstract

Abstract. Phagosomes were purified from human neutrophils ingesting Salmonella typhimurium opsonized with adsorbed normal human serum or with rabbit IgG. Constituents within the phagosome were endogenously labeled by supplying the cells with ~25INa during phagocytosis. Lactoferrin and vitamin B~2 binding protein (TC1 and TC3), markers for specific granules, were present in the phagosomes from neutrophils ingesting S. typhimurium opsonized with IgG but were 3.5-to 5-fold less prominent in phagosomes from cells phagocytosing Salmonella bearing C3 fragments only.In contrast, iodinated azurophilic granule components, most prominently defensins, were the major constituents in phagosomes prepared under both opsonization conditions. Furthermore, labeled complement (CR1 and CR3) and immunoglobulin (FcTRIII) receptors were incorporated in the phagosome regardless of the ligand mediating phagocytosis. These results suggest that the ligand-receptor interactions mediating phagocytosis influence incorporation of neutrophil-specific granule contents into phagosomes.

Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3

“…Immunoglobulins were used as opsonizing ligands because they optimize the incorporation of specific granules (and, thus, hCAP-18) into the phagolysosome. 57 Immunoglobulin-coated latex particles were found not to inhibit the cleavage of hCAP-18 by the serine proteases from azurophil granules. Furthermore, a substantial amount of the hCAP-18 in the cells was present in the phagolysosome, and azurophil granule constituents were found together with hCAP-18 in most examined phagolysosomes.…”

Alterations in the protein composition of maturing phagosomes.

“…Joiner et al recently reported that neutrophil phagocytosis ofparticles opsonized with C3 fragments leads to decreased specific granule-phagosome fusion compared to particles opsonized with antibody (24). As a consequence, phagosomes containing antibody-coated particles may contain more specific granule components than phagosomes containing C3b-coated particles.…”

Intramolecular inhibition of human defensin HNP-1 by its propiece.

“…In resting neutrophils, mature defensins are stored in the azurophil granules and are delivered to phagosomes during phagocytosis (33,34). Extracellular release of mature defensin from phagocytosing neutrophils in vitro is modest (Ͻ 3% of cell content) (35).…”