Leukocyte adhesion-deficient neutrophils fail to amplify phagocytic function in response to stimulation. Evidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis.

Abstract

Stimulation of PMN with inflammatory mediators markedly augments Fc and CR1 receptor-mediated ingestion. However, CDM1/CD18-deficient PMN from three patients with complete leukocyte adhesion deficiency (LAD) failed to recruit phagocytic function in response to phorbol esters, cytokine, or ArgGly-Asp-containing ligand stimulation. Because stimulated ingestion is protein kinase C (PKC)-dependent, our data indicate that LAD PMN exhibit only PKC-independent phagocytosis.

Fcγ-receptors Induce Mac-1 (CD11b/CD18) Mobilization and Accumulation in the Phagocytic Cup for Optimal Phagocytosis

“…Cooperation between Fc␥R and integrins had been suggested by several observations, including the reduced ability of leukocyte adhesion deficiency neutrophils to take up IgG-opsonized particles (10) and the observation that antibodies that block Mac-1 function depressed IgG-mediated phagocytosis without impairing the binding of Fc␥R to its ligands (11). In the case of human neutrophils, these effects could be attributed to the known direct association between Mac-1 and Fc␥RIIIB.…”

“…However, interactions between the two systems have been suggested by various observations. Neutrophils from leukocyte adhesion deficiency syndrome patients, which have mutations in the gene encoding CD18 (9), have a reduced ability to ingest IgG-opsonized red blood cells (IgG-RBC) (10). Moreover, antibodies that block Mac-1 function depressed IgG-mediated phagocytosis without impairing the binding of Fc␥R to its ligands (11).…”

Increased Resistance Against Acute Polymicrobial Sepsis in Mice Challenged with Immunostimulatory CpG Oligodeoxynucleotides Is Related to an Enhanced Innate Effector Cell Response

“…Therefore, it is conceivable that the increase in neutrophil numbers and the elevated surface density of phagocytic receptors contribute to the improved bacterial clearance, which was observed in mice challenged with CpG-ODN. Thus, up-regulation of Mac-1 and Fc␥-receptors may improve phagocytosis of opsonized bacteria by neutrophils in CpG-ODNtreated mice and increased cell surface Mac-1 may facilitate cell recruitment from the circulation to the inflamed peritoneal cavity (40,41).…”

Immune Complex-induced Integrin Activation and L-plastin Phosphorylation Require Protein Kinase A

“…In general, increases in [cAMP] have been found to inhibit fMLP-stimulated PMN activation, as measured by adhesion or respiratory burst activation (30,36,40,41) and have been found to inhibit integrin activation in several cell types (29,42,43). However, Fc␥R-mediated accumulation of cAMP and of PKA at phagosomes has been noted previously (44,45), although this cAMP has been variously interpreted as part of the activation process (44) and a component of the regulation of phagocytosis (45).…”