title: Neutrophils released from the bone marrow by granulocyte colony-stimulating factor sequester in lung microvessels but are slow to migrate.
abstract: Inflammatory mediators such as granulocyte colony-stimulating factor (G-CSF) release polymorphonuclear leukocytes (PMNL) from the bone marrow. This growth factor is used to promote the host response to infection but its effect on the behaviour of leukocytes at the inflammatory site is unclear. This study examined the sequestration and migration of PMNL released from the bone marrow by G-CSF in a model of streptococcal pneumonia. Eight hours following the administration of either human G-CSF (n=6) or saline (n=3) in rabbits, a focal Streptococcus pneumoniae pneumonia was induced and the animals were followed for 2 h. The thymidine analogue 5'-bromo-2'-deoxyuridine (BrdU) was used to label PMNL (PMNL(BrdU)) in the marrow and as a marker of PMNL newly released by the bone marrow. The PMNL(BrdU) in the lung and blood were identified using immunohistochemistry. G-CSF pretreatment elevated the circulating PMNL (3.6+/-0.4 (mean+/-SEM) to 8.3+/-1X10(9) x L(-1), p<0.05) and PMNL(BrdU) (5.4+/-2.1 to 12.5+/-3.1%, p<0.05) counts at 8 h with little further increase caused by the subsequent 2 h pneumonia. These counts did not change in the control group. Morphometric studies of the lung showed that the total number of PMNL sequestered in lung capillaries were increased in the G-CSF group and the percentage of the these PMNL that were BrdU-labelled, was higher than in circulating blood (p<0.05). In the G-CSF group, only 11.2+/-2.6% of the PMNL that migrated into the airspaces were PMNL(BrdU) compared to 50.8+/-8% PMNL(BrdU) in the pulmonary capillaries. In vitro studies showed PMNL(BrdU) released from the bone marrow by G-CSF are less deformable than unlabelled circulating PMNL (p<0.01). It is concluded that granulocyte colony-stimulating factor treatment causes the marrow to release polymorphonuclear leukocytes that preferentially sequester in lung microvessels but are slow to migrate out of the vascular space into the airspace at the pneumonic site.
authors.affiliation: University of British Columbia, Pulmonary Research Laboratory, St Paul's Hospital, Vancouver, Canada.
authors.forename: S F
authors.initials: SF
authors.lastname: van Eeden
authors.forename: E
authors.initials: E
authors.lastname: Lawrence
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: J C
authors.initials: JC
authors.lastname: Hogg
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D001854:Bone Marrow Cells / Q000276:immunology*; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D018821:CD18 Antigens / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D048429:Cell Size / Q000276:immunology; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019041:L-Selectin / Q000032:analysis; D007958:Leukocyte Count; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D011652:Pulmonary Circulation / Q000276:immunology; D011817:Rabbits
chemical_list: D000963:Antimetabolites; D018821:CD18 Antigens; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine