Neutrophil migration in vivo and in vitro in healthy neutropenic subjects.

Migration of polymorphonuclear leukocytes (PMN) was studied in six healthy subjects with neutropenia (peripheral blood neutrophil count less than or equal to 1.5 X 10(9)/1). Determined as migration differentials, chemotactic and chemokinetic responsiveness tended to be higher in the neutropenic group. Despite this slight tendency to increased responsiveness in vitro, migration in vivo proceeded more slowly in the neutropenic group than in the control group: at 12 hours the leukocyte counts in the skin chamber media were significantly lower, whereas at 24 hours they were nearly normal. Our results show that PMN migration in healthy neutropenic subjects is different from that in healthy non-neutropenic subjects. These differences should be taken into account in the evaluation of the role of aberrant PMN migration in the development of infectious episodes in a neutropenic patient.

Polymorphonuclear leucocyte function and previous yersinia arthritis: correlation of enhanced superoxide production with late manifestations.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, and aggregation) were studied in 32 patients with previous yersinia arthritis (YA). PMNs of 11 HLA-B27 positive patients who had chronic or recurrent inflammatory symptoms showed O-2 production significantly higher than that of PMNs of 11 HLA-B27 positive patients without late manifestations. Also, PMNs of both HLA-B27 positive and negative patients tended to show chemotactic and chemokinetic migration rates higher than those of control cells of healthy HLA-B27 negative subjects. These functional aberrations may play a part in the development of the patients' inflammatory symptoms.

Bacterial-lipopolysaccharide-induced release of lactoferrin from human polymorphonuclear leukocytes: role of monocyte-derived tumor necrosis factor alpha.

We have examined the role played by human peripheral blood monocytes in mediating responses of human polymorphonuclear leukocytes (PMN) to bacterial lipopolysaccharide (LPS) in vitro. When incubated with Salmonella typhimurium LPS at 37 degrees C, human PMN suspended in serum-free buffer released the specific granule constituent lactoferrin into the surrounding medium. Release of lactoferrin from PMN varied with the concentration of LPS (1 to 1,000 ng/ml) as well as with the duration of incubation (2 to 60 min) and was not accompanied by significant release of the cytoplasmic enzyme lactate dehydrogenase. LPS-induced release of lactoferrin from PMN was augmented significantly when cell suspensions were supplemented with additional monocytes and lymphocytes. Only monocytes, however, secreted significant amounts of lactoferrin-releasing activity (in a time- and concentration-dependent manner) when incubated separately with LPS. Lactoferrin-releasing activity was heat (80 degrees C for 15 min) labile, eluted after chromatography on Sephadex G-100 with an apparent molecular weight of approximately 60,000, and was inhibited by antibodies to tumor necrosis factor alpha. Thus, LPS-induced noncytotoxic release of lactoferrin from human PMN suspended in serum-free buffer is mediated, at least in part, by tumor necrosis factor alpha derived from contaminating monocytes.

Polymorphonuclear leucocyte function and previous yersinia arthritis: enhanced chemokinetic migration and oxygen radical production correlate with the severity of the acute disease.

Polymorphonuclear leucocyte (PMN) functions (migration in vitro, chemiluminescence, O-2 production, binding of chemotactic peptide, and aggregation) were studied in HLA-B27 positive patients with previous yersinia arthritis (YA). PMNs of patients whose disease had been severe showed chemokinetic and chemiluminescence responses significantly higher than the PMNs of those with a mild disease. The results support the view that enhanced PMN function contributes to inflammatory symptoms in patients with YA.

Neutrophil migration in vivo: analysis of a skin window technique.

The applicability of a skin chamber technique for the quantitation of neutrophil migration in vivo was studied in healthy subjects. Skin lesions were generated on lower abdominal skin by separating epidermis from dermis by suction. In 23 subjects the mean chamber cell count at 24 h was 20.9 X 10(6)/cm2 of skin lesion area, and 97.5% of the cells were neutrophils. An analysis of the variance in up to 8 parallel chambers in 10 subjects supported the use of 4 simultaneous replicates. Reproducibility in consecutive experiments was studied by testing 9 persons twice; the results were found to agree closely. Kinetic studies were performed in 15 subjects. The method is useful for the in vivo study of diseases and medications thought to affect leukocyte function.

Enhanced neutrophil migration in vivo HLA B27 positive subjects.

Chemotaxis of polymorphonuclear leucocytes in vivo was studied in patients with previous yersinia arthritis and in healthy subjects with or without HLA B27 by means of a skin chamber technique. Irrespective of previous arthritis the number of neutrophils in the chamber media was significantly higher in HLA B27 positive subjects than in those without HLA B27. The amounts of prostaglandins E2, F2 alpha, and 6-keto-F1 alpha in the chamber media correlated positively with the corresponding cell counts. The present results give credence to the view that the hyperreactive neutrophils and the vasodilatory prostaglandins produced by them can together trigger a vicious circle which results in increased inflammatory symptoms in patients with yersinia arthritis who have HLA B27 as compared with those who lack this antigen.

Exaggerated inflammatory responsiveness plays a part in the pathogenesis of HLA-B27 linked diseases--hypothesis.

Ankylosing spondylitis, acute anterior uveitis and reactive arthritides, including enteroarthritis and uroarthritis , are all associated with the human leucocyte antigen (HLA) B27. The pathogenesis of these diseases is not known, but it may involve inflammatory responsiveness of the host. In an acute inflammatory reaction, neutrophils are considered to cause tissue injury by both liberating lysosomal enzymes and generating toxic oxygen-derived free radicals. Furthermore, they may regulate both capillary permeability and the rate of vasodilatation at the site of inflammation. Evidence has accumulated that neutrophil responses to a phlogistic stimulus are enhanced in HLA-27 positive subjects. We suggest that hyperreactive neutrophils trigger a vicious circle of inflammation and render the subjects susceptible to exaggerated tissue injury.