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Polymorphonuclear leukocyte (PMN) migration in streptococcal pneumonia: comparison of older PMN with those recently
E Lawrence1, S Van Eeden, D English
1University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Abstract:
In acute bacterial pneumonia, polymorphonuclear leukocytes (PMN) sequester in the lung and migrate into the alveolar airspaces. These local events are accompanied by a systemic response that includes release of PMN from the bone marrow into the circulation. The present study was designed to compare the sequestration and migration of these newly released PMN with those already in the circulation in a model of acute streptococcal pneumonia in rabbits. PMN were labeled in the mitotic pool in the marrow by administration of 5'-bromo-2'-deoxyuridine (BrdU 100 mg/kg) and the labeled cells were detected in blood and tissues by immunohistochemistry. The proportion of BrdU-labeled PMN (PMN BrdU) that sequestered and migrated in the lung tissue infected with Streptococcus pneumoniae and the uninfected lung was measured using morphometric techniques. The results show an increase in the proportion of PMN BrdU (6.0 +/- 1.0% to 17.3 +/- 3.8%, P<0.05) in the circulation 5 h following the induction of a pneumonia and the PMN expressed a higher concentration of L-selectin (9.3 +/- 0.7 to 14.9 +/- 0.8 MFI, P<0.05). The proportion of PMN BrdU in the control tissue was not different from the proportion in the systemic circulation (11.4 +/- 1.6%). The PMN BrdU increased in the pneumonic site at 5 h (19.9 +/- 3.4%, P<0.05) and 8 h (26.6 +/- 1.5%, P<0.05) after treatment. Only 2.8 +/- 0.3% and 2.8 +/- 0.6% of the PMN that migrated into the airspace at 5 and 8 h were PMN BrdU. We conclude that PMN released into the circulation as part of the systemic response to a local streptococcal pneumonia sequester normally but may be slow to migrate into the airspaces at the inflammatory site.
Insights
Newly released polymorphonuclear leukocytes (PMN) in pneumonia sequester normally but migrate slowly into airspaces. This study tracked labeled PMN in rabbits with streptococcal pneumonia to understand their lung infiltration dynamics.
Area of Science:
- Immunology
- Pulmonology
- Microbiology
Background:
- Acute bacterial pneumonia involves polymorphonuclear leukocytes (PMN) sequestering in the lungs and migrating into alveolar spaces.
- A systemic response includes the release of new PMN from bone marrow into circulation during pneumonia.
Purpose of the Study:
- To compare the sequestration and migration of newly released PMN versus circulating PMN in a rabbit model of acute streptococcal pneumonia.
- To investigate the kinetics of PMN infiltration into lung tissue and alveolar spaces following bacterial infection.
Main Methods:
- Rabbits with induced Streptococcus pneumoniae pneumonia were used to model acute bacterial pneumonia.
- Newly produced PMN were labeled in the bone marrow using 5'-bromo-2'-deoxyuridine (BrdU).
- Immunohistochemistry and morphometric techniques quantified labeled PMN (PMN BrdU) in circulation, lung tissue, and alveolar spaces at different time points.
Main Results:
- The proportion of PMN BrdU in circulation increased significantly 5 hours post-pneumonia induction, with elevated L-selectin expression.
- PMN BrdU proportion increased in pneumonic lung tissue at 5 and 8 hours.
- However, PMN BrdU constituted a small fraction (2.8%) of PMN migrating into alveolar airspaces at 5 and 8 hours.
Conclusions:
- PMN released into circulation during streptococcal pneumonia sequester appropriately in the lung.
- Newly released PMN may exhibit delayed migration into the alveolar airspaces at the inflammatory site compared to resident PMN.