Submitted on January 8, 2003
Accepted on October 8, 2003
Depletion of Pulmonary Intravascular Macrophages Inhibits Acute Lung Inflammation
Baljit Singh1*, Jacqueline W. Pearce1, Lakshman N. Gamage1, Kyathanahalli Janardhan1, and Sarah Caldwell1
1 Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
* To whom correspondence should be addressed. E-mail: baljit.singh{at}usask.ca.
Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared to non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and post-embedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 hours of treatment (p<0.05). Finally, PIMs contain TNF-
and their depletion reduces cells positive for IL-8 (p<0.05) and TNF- (p<0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. Majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin (p<0.05). These novel data show that PIMs, as the source of TNF-, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to their ability to recruit PIMs.
