title: A hampered chemoattractant-induced cytoskeletal rearrangement in granulocytes of patients with unexplained severe chronic and relapsing infections of the upper and lower airways. In vitro restoration by G-CSF exposure.
abstract: Granulocytes play a major role in host defense against bacterial infections. Severe inborn defects in granulocyte function are associated with fulminant bacterial infections in early childhood. Subtle disturbances in granulocyte function might contribute to an enhanced susceptibility to bacterial infections in adulthood. We investigated chemoattractant (N-formyl-methionyl-leucyl-phenylalanine, fMLP and casein) induced cytoskeletal rearrangements (polarization) of blood granulocytes in 77 adults with chronic and recurrent therapy-resistant infections of the upper and lower airways. These infections could not be explained by B- and/or T-cell defects or local anatomic abnormalities. Besides polarization, chemotaxis of blood granulocytes was measured in 33 patients, as well as granulocyte superoxide production in eight patients. The chemoattractant-induced cytoskeletal rearrangement in patient blood granulocytes was significantly lower as compared to healthy control values with both fMLP and casein as stimuli. About two-thirds of the patients showed a defective polarization response to fMLP. Granulocyte colony-stimulating factor (G-CSF) when added in vitro corrected the defective polarization responses; responses in the normal range were not enhanced. The chemotactic motility of patient blood granulocytes was also slightly, but significantly lowered. However, it did not correlate to the lowered polarization. Granulocyte superoxide production was comparable in patients and in healthy controls. Our data thus show that subtle abnormalities in chemoattractant-induced cytoskeletal and motile function of blood granulocytes are frequent in patients with severe therapy-refractory bacterial infections of the upper and lower airways.
authors.affiliation: Department of Immunology, Eramus University and University Hospital Dijkzigt, Rotterdam, The Netherlands.
authors.forename: P M J
authors.initials: PM
authors.lastname: Kalkman
authors.forename: W J
authors.initials: WJ
authors.lastname: Fokkens
authors.forename: H J
authors.initials: HJ
authors.lastname: de Wit
authors.forename: J P
authors.initials: JP
authors.lastname: van de Merwe
authors.forename: H
authors.initials: H
authors.lastname: Hooijkaas
authors.forename: J M W
authors.initials: JM
authors.lastname: van Haarst
authors.forename: H C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: H A
authors.initials: HA
authors.lastname: Drexhage
mesh_terms: D000328:Adult; D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D002364:Caseins / Q000494:pharmacology; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002614:Chelating Agents / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D002908:Chronic Disease; D003599:Cytoskeleton / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012008:Recurrence; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology
chemical_list: D002364:Caseins; D002614:Chelating Agents; D002630:Chemotactic Factors; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine