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Changes in gravity inhibit lymphocyte locomotion through type I collagen
N R Pellis1, T J Goodwin, D Risin
1Biotechnology Program, National Aeronautics and Space Administration (NASA), Lyndon B. Johnson Space Center, Houston, Texas 77058, USA.
Insights
Simulated microgravity impairs human lymphocyte locomotion through collagen, suggesting non-stress-related immune changes. Recovery is slow, indicating potential long-term effects on immune cell function.
Area of Science:
- Immunology
- Cell Biology
- Space Medicine
Background:
- Immunity depends on lymphocyte circulation through various tissues.
- Lymphocyte interstitial migration is crucial for immune surveillance.
- Microgravity is a potential cause of immunosuppression.
Purpose of the Study:
- Investigate microgravity's effects on human lymphocyte function in vitro.
- Characterize mechanisms of microgravity-induced immunosuppression.
- Assess lymphocyte locomotion and activation under simulated microgravity.
Main Methods:
- Used a rotating-wall vessel (RWV) culture system to simulate microgravity.
- Assayed peripheral blood lymphocyte locomotion through Type I collagen.
- Evaluated lymphocyte viability, activation, and adhesion molecule expression.
Main Results:
- Simulated microgravity inhibited lymphocyte locomotion through Type I collagen.
- Lymphocytes showed impaired recovery of locomotion after RWV culture.
- RWV culture blunted lymphocyte response to phytohemagglutinin activation.
- Pre-activation with anti-CD3/IL-2 preserved locomotion in RWV.
Conclusions:
- Microgravity induces non-stress-related changes in lymphocyte function, affecting locomotion.
- Simulated microgravity alters lymphocyte activation states and adhesion molecule expression.
- The RWV system serves as a model to study microgravity's impact on lymphocyte movement.
- Findings suggest microgravity-induced changes in cell function may critically impact immunity.
Abstract:
Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes by ceasing locomotion through model interstitium. These in vitro investigations suggest that microgravity induces non-stress-related changes in cell function that may be critical to immunity. Preliminary analysis of locomotion in true microgravity revealed a substantial inhibition of cellular movement in Type I collagen. Thus, the rotating-wall vessel culture system provides a model for analyzing the microgravity-induced inhibition of lymphocyte locomotion and the investigation of the mechanisms related to lymphocyte movement.