E. coli pneumonia induces CD18-independent airway neutrophil migration in the absence of increased lung vascular permeability.
We examined the relationship between neutrophil [polymorphonuclear leukocyte (PMN)] influx and lung vascular injury in response to Escherichia coli pneumonia. We assessed lung tissue PMN uptake by measuring myeloperoxidase and transvascular PMN migration by determining PMN counts in lung interstitium and bronchoalveolar lavage fluid (BALF) in mice challenged intratracheally with E. coli. Lung vascular injury was quantified by determining microvessel filtration coefficient (Kf,c), a measure of vascular permeability. We addressed the role of CD18 integrin in the mechanism of PMN migration and lung vascular injury by inducing the expression of neutrophil inhibitory factor, a CD11/CD18 antagonist. In control animals, we observed a time-dependent sixfold increase in PMN uptake, a fivefold increase in airway PMN migration, and a 20-fold increase in interstitial PMN uptake at 6 h after challenge. Interestingly, Kf,c increased minimally during this period of PMN extravasation. CD11/CD18 blockade reduced lung tissue PMN uptake consistent with the role of CD18 in mediating PMN adhesion to the endothelium but failed to alter PMN migration in the tissue. Moreover, CD11/CD18 blockade did not affect Kf,c. Analysis of BALF leukocytes demonstrated diminished oxidative burst compared with leukocytes from bacteremic mice, suggesting a basis for lack of vascular injury. The massive CD11/CD18-independent airway PMN influx occurring in the absence of lung vascular injury is indicative of an efficient host-defense response elicited by E. coli pneumonia.
Ong
Evan S
ES
Dept. of Pharmacology, College of Medicine, Univ. of Illinois, 835 S. Wolcott Ave., Chicago, IL 60612-7343, USA. xgao@uic.edu
Gao
Xiao-Pei
XP
Xu
Ning
N
Predescu
Dan
D
Rahman
Arshad
A
Broman
Michael T
MT
Jho
David H
DH
Malik
Asrar B
AB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018821:CD18 Antigens / Q000378:metabolism*; D002199:Capillary Permeability; D002465:Cell Movement; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D004927:Escherichia coli Infections / Q000401:mortality; D006023:Glycoproteins / Q000378:metabolism; D015801:Helminth Proteins / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology*; D011014:Pneumonia / Q000150:complications / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D011652:Pulmonary Circulation; D011654:Pulmonary Edema / Q000209:etiology; D016897:Respiratory Burst
D018821:CD18 Antigens; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D006023:Glycoproteins; D015801:Helminth Proteins; D008565:Membrane Proteins; C086581:NIF protein, Ancylostoma caninum