Association of aberrant F-actin formation with defective leukocyte chemotaxis and recurrent pyoderma.
A young boy with recurrent skin infections and slow wound healing was shown to have an isolated leukocyte chemotactic defect. The chemotactic abnormality was persistent throughout the observation period, could be demonstrated both in vivo and in vitro, and was not related to known causes of chemotactic defects. To investigate the underlying pathogenetic mechanism for this abnormality, the patient's polymorphonuclear (PMN) leukocytes were studied for their ability to respond to the chemotactic peptide N-formyl-methionylleucylphenylalanine (FMLP). The patient's leukocytes were able to bind FMLP normally and responded appropriately to the stimulus as shown by a rise in intracellular calcium after binding. However, his PMN leukocytes demonstrated abnormalities in the formation and disassembly of filamentous actin (F-actin), an important structural component in cell locomotion. Since the formation and disassembly of F-actin are important in the recycling of actin and crucial in the cell movement, the observed abnormalities may account for the disorder of chemotaxis seen in this patient. The findings in this case resemble the syndrome of neutrophil actin dysfunction. However, observed differences, including a much milder clinical disease, distinguish between these two clinical entities.
Jung
L K
LK
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
D000199:Actins / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D002675:Child, Preschool; D006801:Humans; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D011711:Pyoderma / Q000276:immunology* / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000032:analysis; D012008:Recurrence
D000199:Actins; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine