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Granulocyte-macrophage colony stimulating factor potentiates human polymorphonuclear leukocyte aggregation responses
P Conti1, M Reale, R C Barbacane
1Immunology Division, University of Chieti, Italy.
Abstract:
Polymorphonuclear leukocytes (PMN) are known to be activated by several lymphokines and can be induced to release lysosomal enzymes, prostaglandins (PG), thromboxanes (TX) and lipoxygenase products that may be involved in PMN aggregation responses during inflammatory reactions. Granulocyte-macrophage colony stimulating factor (GM-CSF), a glycoprotein cytokine released by immunocompetent cells, has been found to prime neutrophil responses, such as increased cell aggregation after exposure to various biological stimulants. In this study, we examined the effects of the cytokine GM-CSF on human neutrophilic aggregation stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) and its influence on the production of various arachidonic acid metabolites. Neutrophil aggregation of purified PMNs was measured by the percent change in light transmission in a standard aggregometer, and the arachidonic acid products leukotriene B4 (LTB4) and thromboxane A2 (TXA2) were quantified by radioimmunoassay. We found that GM-CSF and other cytokines, used alone, did not cause any significant increase in aggregation of the PMN. However, prior exposure of PMN to GM-CSF markedly increased the aggregation induced by FMLP as opposed to that detected with PMN stimulated with only FMLP. This priming effect was not observed with PMN preincubated with interleukin-1 (IL-1), tumor necrosis factor (TNF) or interleukin-6 (IL-6). In addition, GM-CSF and IL-6 both failed to stimulate the production of LTB4 and TXA2, products which are known to induce PMN aggregation. These findings provide new evidence suggesting that GM-CSF facilitates the action of FMLP on the adhesion dependent cellular functions of the inflammatory response, serving as an important co-factor in neutrophil aggregation.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) primes human neutrophils for enhanced aggregation when stimulated by FMLP. This cytokine acts as a co-factor, facilitating inflammatory responses without directly inducing aggregation or producing inflammatory mediators.
Area of Science:
- Immunology
- Cellular Biology
- Inflammation Research
Background:
- Polymorphonuclear leukocytes (PMNs) release inflammatory mediators like prostaglandins and thromboxanes upon activation.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine known to prime neutrophils for enhanced responses.
- Neutrophil aggregation is a key process in inflammatory reactions.
Purpose of the Study:
- To investigate the effect of GM-CSF on human neutrophil aggregation induced by N-formyl-methionyl-leucyl-phenylalanine (FMLP).
- To assess GM-CSF's influence on the production of arachidonic acid metabolites, such as leukotriene B4 (LTB4) and thromboxane A2 (TXA2).
- To compare the priming effect of GM-CSF with other cytokines like IL-1, TNF, and IL-6.
Main Methods:
- Purified human PMNs were used to measure aggregation via light transmission changes in an aggregometer.
- Neutrophil aggregation was stimulated using FMLP.
- Production of LTB4 and TXA2 was quantified using radioimmunoassay.
Main Results:
- GM-CSF alone did not induce significant PMN aggregation.
- Prior exposure to GM-CSF markedly enhanced FMLP-induced PMN aggregation compared to FMLP stimulation alone.
- This priming effect was not observed with IL-1, TNF, or IL-6, and GM-CSF did not stimulate LTB4 or TXA2 production.
Conclusions:
- GM-CSF acts as a priming agent, significantly potentiating FMLP-induced neutrophil aggregation.
- GM-CSF facilitates FMLP's action on adhesion-dependent inflammatory functions of neutrophils.
- GM-CSF serves as a crucial co-factor in neutrophil aggregation during inflammatory processes.