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IL-1beta stimulation induces paracrine regulation of PMN function and apoptosis
P S Grutkoski1, R D'Amico, A Ayala
1Rhode Island Hospital, Division of Surgical Research, Providence 02903, USA.
Abstract:
Polymorphonuclear leukocytes (PMN) play a crucial role in the primary immunological defense against infectious agents. PMN activation and function is influenced in a paracrine manner by cytokines and bacterial products. While cell-cell communication has been demonstrated between PMN and other cell types, little data is available addressing PMN-PMN communication. Therefore, the aim of this study was to determine whether PMN were able to affect PMN function in vitro in a cell-contact independent manner, and whether IL-1beta influenced this effect. Conditioned medias (CM) were prepared by incubating PMN in HBSS +/- IL-1beta for 1-4 h. Incubation of fresh PMN in these conditioned medias had little or no effect on the expression of cell surface FcgammaR expression or oxidative metabolism. However, incubation of PMN in CM-IL1beta, but not control CM, increased phagocytotic activity and suppressed apoptosis. Additionally, CM-IL1beta, but not control CM, slowed the changes in Mac-1 and CR1 cell surface expression that occurred in HBSS within 2 h of incubation. Finally, control CM down-regulated the cell surface expression of PSGL-1; an effect that was not observed with CM-IL1beta. In conclusion, we demonstrate that PMN are able to communicate with and influence the immunological function of other PMN independent of cell-cell contact, and that this influence is regulated by cytokines such as IL-1beta. The major impact of this paracrine regulation is to down-regulate PMN apoptosis with the potential for an upregulated inflammatory response.
Insights
Polymorphonuclear leukocytes (PMN) communicate and influence each other's function without direct cell contact. Interleukin-1 beta (IL-1beta) regulates this paracrine signaling, suppressing PMN apoptosis and potentially increasing inflammation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMN) are vital for innate immunity against pathogens.
- PMN function is modulated by cytokines and bacterial products.
- Limited data exists on PMN-to-PMN communication.
Purpose of the Study:
- To investigate if PMN can influence PMN function independently of cell contact.
- To determine the role of IL-1beta in PMN-PMN communication.
Main Methods:
- Prepared conditioned media (CM) from PMN incubated with or without IL-1beta.
- Incubated fresh PMN in CM.
- Assessed cell surface receptor expression (FcgammaR, Mac-1, CR1, PSGL-1), oxidative metabolism, phagocytosis, and apoptosis.
Main Results:
- CM-IL1beta enhanced PMN phagocytosis and suppressed apoptosis.
- CM-IL1beta slowed changes in Mac-1 and CR1 expression.
- Control CM reduced PSGL-1 expression, an effect not seen with CM-IL1beta.
Conclusions:
- PMN communicate and modulate each other's function via paracrine signaling.
- IL-1beta regulates this communication, primarily by reducing PMN apoptosis.
- This paracrine regulation may lead to an amplified inflammatory response.