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

• Published in: The Journal of clinical investigation 1991-08, Vol.88 (2), p.588-597
• Main Authors: GRESHAM, H. D, GRAHAM, I. L, ANDERSON, D. C, BROWN, E. J
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; Antigens, CD - physiology; Biological and medical sciences; CD18 Antigens; Complement C4b - immunology; Granulomatous Disease, Chronic - immunology; Humans; Immunoglobulin G - immunology; Investigative techniques, diagnostic techniques (general aspects); Leukocyte-Adhesion Deficiency Syndrome; Macrophage-1 Antigen - physiology; Medical sciences; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - immunology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phagocytosis; Phorbol 12,13-Dibutyrate - pharmacology; Protein Kinase C - physiology; Protein Kinases - physiology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI115343

Stimulation of PMN with inflammatory mediators markedly augments Fc and CR1 receptor-mediated ingestion. However, CD11/CD18-deficient PMN from three patients with complete leukocyte adhesion deficiency (LAD) failed to recruit phagocytic function in response to phorbol esters, cytokine, or Arg-Gly-Asp-containing ligand stimulation. Because stimulated ingestion is protein kinase C (PKC)-dependent, our data indicate that LAD PMN exhibit only PKC-independent phagocytosis. The defect in PKC-dependent ingestion is specific for CD11b/CD18 and not secondary to the chronic or recurrent infections which occur in this disease. The LAD phenotype for phagocytic function can be reproduced in normal PMN by the anti-CD11b MAbs OKM1 and OKM10. In contrast, MAb Mo1 (anti-CD11b) and MAb IB4 (anti-CD18) inhibit both CD11b/CD18-dependent and -independent mechanisms of ingestion by normal PMN. Their ability to inhibit CD11b/CD18-independent ingestion may be mediated by cAMP, as shown by experiments with a protein kinase A inhibitor HA1004 and by direct measurement of cAMP levels in immune complex- and FMLP-stimulated PMN. These data indicate that CD11b/CD18-independent and -dependent mechanisms of phagocytosis exist and that some effects of anti-CD11b/CD18 MAbs may be mediated by alterations in cAMP levels.