Neutrophil-mediated lung permeability and host defense proteins.
Neutrophil recruitment to the alveolar space is associated with increased epithelial permeability. The present study investigated in mice whether neutrophil recruitment to the lung leads to accumulation of plasma-derived host defense proteins in the alveolar space and whether respiratory burst contributes to this increase in permeability. Albumin, complement C1q, and IgM were increased in bronchoalveolar lavage (BAL) fluid 6 h after intratracheal LPS challenge. Neutrophil depletion before LPS treatment completely prevented this increase in BAL fluid protein concentration. Respiratory burst was not detected in neutrophils isolated from BAL fluid, and BAL proteins were increased in mice deficient in a key subunit of the respiratory burst apparatus, gp91(phox), similar to wild-type mice. Neutrophil recruitment elicited by intratracheal instillation of the chemokines macrophage inflammatory protein-2 and keratinocyte-derived chemokine was also accompanied by accumulation of albumin, C1q, and IgM. During neutrophil recruitment to the alveolar space, epithelial permeability facilitates delivery of host defense proteins. The observed increase in epithelial permeability requires recruitment of neutrophils, but not activation of the respiratory burst, and occurs with chemokine-induced neutrophil migration independent of LPS exposure.
Kantrow
Stephen P
SP
Section of Pulmonary and Critical Care Medicine, Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA. skantr@lsuhsc.edu
Shen
Zhiwei
Z
Jagneaux
Tonya
T
Zhang
Ping
P
Nelson
Steve
S
D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007075:Immunoglobulin M / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016897:Respiratory Burst; D012709:Serum Albumin / Q000378:metabolism*
D054426:Chemokine CXCL2; D018925:Chemokines; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012709:Serum Albumin; C074302:keratinocyte-derived chemokines; D015922:Complement C1q; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases