Table 2.

Outline of experimental platforms, cell types, durations, and results in the literature of macrophage microgravity research.

Experiment platform	Paper	Cell type	Time in µg	Results
Clinorotation (simulated µg)	Shi 2020	Primary mouse	12 d	Macrophage differentiation from hematopoietic progenitor cells and functional polarization impaired in µg; RAS/ERK/NFκB pathway gravisensitive
	Wang 2015	Primary mouse	24 h	Simulated µg activates p38 MAPK-C/EBPβ pathway; increased arginase expression; upregulated IL-6, downregulated IL-12B
	Brungs 2015	NR8383	4 h	Reduced ROS production in µg; diminished Syk phosphorylation; NFκB nuclear translocation unaltered
	Paulsen 2015	BV-2 microglial cells; U937; Primary human	1 d; 3 d; 5 d	Reduced ICAM-1 expression in BV-2 cells; increased ICAM-1 expression in U937 and primary human macrophages
	Wang 2014	RAW 264.7; Primary mouse	24 h	LPS-induced TNF-α expression in µg reduced, but not IL-1β; increased HSF-1 in µg; nuclear translocation of NFκB unchanged
	Adrian 2013	NR8383	30–180 m	ROS release is reduced in µg, responding rapidly and reversibly
	Paulsen 2010	U937	5 m	Non-stimulated macrophages had enhanced tyrosine phosphorylation and c-jun activation; PMA-stimulated macrophages had reduced tyrosine phosphorylation and c-jun activation
	Maier 2006	U937	24 h; 72 h	Upregulation of hsp70; inhibited proliferation; altered cytokine secretion in µg
	Hsieh 2005	RAW 264.7	2 d	Reduction in nitric oxide and cytokine production; flavonoids compensated for loss of macrophage function in 3D culture
	Maccarrone 2003	U937	2–72 h	No expression of active 5-LOX or apoptosis, in contrast to lymphocytes
	Hashemi 1999	Primary human	24 h	Normal IL-1 synthesis
Random position machine (simulated µg)	Meloni 2006	J-111	1 h; 24 h	Cell motility severely reduced in µg; actin, tubulin, and vinculin structures affected
Limb suspension (simulated µg)	Liu 2015	Primary rat	28 d	µg increased monocyte recruitment, E-selectin and MCP-1 expression, and NFκB activation in abdominal aorta
Suborbital/sounding rocket (real µg)	Thiel 2019	Primary Human	353 s	µg induces cell geometry changes, rapid cytoskeleton reorganization, and rapid adaptation of the cytoskeleton
	Vogel 2019	U937	300 s	HIF-1 differently regulated in altered gravity; some genes have rapid response and adaptation, others altered only after 5 min. in µg
	Thiel 2018	U937	300 s	Transcriptome greatly altered in µg; 99.43% of all initially altered transcripts adapted after 5 min.
	Paulsen 2015	U937	378 s	No detectable effect on ICAM-1 mRNA expression
Parabolic flight (real µg)	Vogel 2019	U937	20 s	HIF-1 differently regulated in altered gravity; some genes have rapid response and adaptation, others altered only after 5 min. in µg
	Thiel 2018	U937	20 s	Transcriptome greatly altered in µg; 99.43% of all initially altered transcripts adapted after 5 min.
	Paulsen 2015	BV-2 microglial cells; U937; Primary human	20 s	Rapid, reversible downregulation of ICAM-1 in BV-2 cells; upregulation of ICAM-1 in differentiated U937 cells; Primary human inconclusive
	Adrian 2013	NR8383	22 s	ROS release is reduced in µg, responding rapidly and reversibly
	Paulsen 2010	U937	20 s	1.3-fold increased MEK phosphorylation; rapid p53 phosphorylation in non-stimulated U937 cells
	Armstrong 1995	B6MP102	20 s	Macrophages respond to µg within 8 s, with increased cell spreading
Spaceflight (real µg)	Shi 2020	Primary mouse	12 d	Macrophage differentiation from hematopoietic progenitor cells and functional polarization impaired in µg; RAS/ERK/NFκB pathway gravisensitive
	Tauber 2017	Primary human	11 d; 30 d	Decreased ICAM-1 and surface-bound fucose; CD18 and CD14 surface expression unaltered
	Thiel 2017	NR8383	15 m	Immediate oxidative burst inhibition followed by extremely rapid adaptation to µg
	Paulsen 2015	U937	5 d	Upregulation of ICAM-1 in differentiated U937 cells
	Paulsen 2014	U937	5 d	Disturbed actin, disorganized tubulin, and reduced CD18, CD36, MHC-II expression in µg
	Crucian 2011	Primary human (blood sample)	13–16 d	Inflammatory phenotype and cytokine production impacted by spaceflight; LPS-stimulated cells showed reduced IL-6, TNF-α, IL-10, and increased IL-1b in µg
	Meloni 2011	J-111	24 h	Severe reduction in motility attributed to disruption of cytoskeleton; actin, tubulin, vinculin distribution affected
	Baqai 2009	Primary mouse (spleen sample)	13 d	Spaceflight can increase anti-inflammatory mechanisms; altered response to LPS stimulation; reduced monocyte/macrophage count; upregulated ROS genes post-flight
	Kaur 2005	Primary human (blood sample)	5–11 d	Monocytes had reduced phagocytic ability, oxidative burst, and degranulation after spaceflight
	Hatton 1999	U937	9 d	Kinetics of protein kinase C are modified during spaceflight.
	Chapes 1999	Primary rat (peritoneal sample)	10 d	Enhanced secretion of TNF, IL-6, and nitric oxide
	Hashemi 1999	Primary human	22 h; 25 h	Normal IL-1 synthesis
	Armstrong 1995	B6MP102	6–8 d	Increased macrophage proliferation; reduced IL-6 secretion; reduced differentiation
	Chapes 1992	B6MP102	6 d; 9 d	Greater secretion of IL-1 and TNF of LPS-stimulated macrophages in µg

µg microgravity, s second, m minute, h hour, d day.