Annexin I degradation in bronchoalveolar lavage fluids from healthy smokers: a possible mechanism of inflammation.
Annexin I is a glucocorticoid-inducible, phospholipase A2-inhibitory protein and is proposed to have an anti-inflammatory role. Although annexin I is a cytosolic protein, it is found extracellularly in secreted fluids such as semen. We have examined the expression of annexin I in bronchoalveolar lavage fluids (BALF) from smokers and nonsmokers to investigate the role of annexin I in the airway. We find that annexin I is secreted in BALF. This secretion is not due to cell death or damage, because a cytosolic protein, 3-phosphoglycerate kinase, is not seen in BALF. We observed that BALF from smokers (n = 10) had high protein concentrations as compared with BALF from nonsmokers (n = 11). Annexin I levels were higher in BALF from smokers compared with nonsmokers. However, in smokers, annexin I was exclusively found in the Mr 34,000 form that lacks the Mr 3,000 N-terminal anti-inflammatory peptide. In nonsmokers, both the Mr 37,000 native annexin I and the Mr 34,000 proteolytically cleaved form are present, with the Mr 37,000 form being most abundant. The NH2-terminal Mr 3,000 peptide of annexin I exhibits anti-inflammatory actions (G. Cirino et al, Br. J. Pharmacol., 108: 573-574, 1993). Previous studies have implicated neutrophil elastase as the protease cleaving annexin I to the Mr 34,000 protein. We observed increased elastase levels in BALF from smokers. However, we find no correlation between bronchial sample percent of neutrophils in BALF and the relative amount of the Mr 34,000 band generated. Our data clearly demonstrate that annexin I is degraded in BALF from smokers, and we propose that proteolytic cleavage of annexin I in BALF from smokers may be a mechanism by which polymorphonuclear neutrophils infiltrate sites of inflammation; thus, inactivation of annexin I in smokers' lungs may lead to chronic and uncontrolled inflammation.
Vishwanatha
J K
JK
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha 68198-4525, USA.
Davis
R G
RG
Rubinstein
I
I
Floreani
A
A
D000818:Animals; D017305:Annexin A1 / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D019272:Leukocyte Elastase / Q000378:metabolism; D008970:Molecular Weight; D009504:Neutrophils / Q000502:physiology; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D012907:Smoking / Q000378:metabolism*
D017305:Annexin A1; D011506:Proteins; D019272:Leukocyte Elastase