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Polymorphonuclear leukocyte transit times in bone marrow during streptococcal pneumonia
T Terashima1, B Wiggs, D English
1Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Abstract:
The release of polymorphonuclear leukocytes (PMN) from the bone marrow (BM) is a hallmark of acute inflammatory conditions. BM stimulation may increase the toxic potential of these newly released PMN and influence their behavior at inflammatory sites. The present study was designed to measure the transit time of PMN in the mitotic and postmitotic pools of the BM in rabbit using 5'-bromo-2'-deoxyuridine (BrdU). Blood samples were obtained at 2- to 24-h intervals from 24 to 192 h after a single BrdU injection, and BrdU-positive PMN (PMNBrdU) was detected as they appear in the circulating blood, using immunohistochemistry. The intensity of nuclear staining for BrdU was used to define a single generation of PMN and graded as either weakly (G1), moderately (G2), or highly (G3) stained. The mean +/- SE transit time of PMNBrdU through the BM was 95.6 +/- 3.6 h, with 51.1 +/- 5.9 h in the mitotic and 65.4 +/- 5.4 h in the postmitotic pool. Streptococcus pneumoniae instillation in the lung (n = 3) shortened the transit time of PMN through the BM to 54.0 +/- 2.6 h with a shorter time in both the mitotic (36.2 +/- 5.7 h) and the postmitotic pool 34.6 +/- 0.8 h). All these values were shorter than the control values (P < 0.05). We conclude that Streptococcus pneumoniae shortens the transit time of PMN in the mitotic and postmitotic pools in the marrow, which may result in the release of immature PMN with higher levels of lysosomal enzymes into the circulation.
Insights
Bacterial infection significantly reduces the time polymorphonuclear leukocytes (PMN) spend in the bone marrow (BM). This accelerated release may lead to immature PMN entering circulation, potentially increasing inflammation.
Area of Science:
- Hematology
- Immunology
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMN) are crucial for acute inflammation.
- Bone marrow (BM) stimulation can alter PMN toxicity and behavior.
- Understanding PMN transit time in BM is key to inflammatory response.
Purpose of the Study:
- To measure PMN transit time in the mitotic and postmitotic pools of rabbit bone marrow.
- To investigate the effect of bacterial infection on PMN transit time.
Main Methods:
- Utilized 5'-bromo-2'-deoxyuridine (BrdU) labeling to track PMN.
- Collected blood samples at intervals post-BrdU injection.
- Detected BrdU-positive PMN (PMNBrdU) using immunohistochemistry.
- Quantified BrdU staining intensity to define PMN generations (G1, G2, G3).
Main Results:
- Mean PMN transit time through BM was 95.6 hours (51.1h mitotic, 65.4h postmitotic).
- Streptococcus pneumoniae infection shortened overall BM transit time to 54.0 hours (36.2h mitotic, 34.6h postmitotic).
- Infected PMN transit times were significantly shorter than controls (P < 0.05).
Conclusions:
- Streptococcus pneumoniae accelerates PMN transit through both mitotic and postmitotic bone marrow pools.
- This expedited release may result in immature PMN entering circulation.
- Immature PMN may possess elevated lysosomal enzyme levels, influencing inflammatory responses.