Related Experiment Videos
Eicosanoid production by peritoneal and splenic macrophages in mice depleted of bone marrow by 89Sr
Abstract:
Previous studies showed that the prostaglandin-forming macrophages (M phi) induced in the spleens of CBA/J mice by intraperitoneal administration of Corynebacterium parvum (CP) could not be demonstrated following the depletion of bone marrow and blood monocytes with 89Sr. The present study compares prostaglandin E2 (PGE2), leukotriene C4 (LTC4), and LTB4 release by splenic and resident peritoneal M phi in 89Sr-treated mice and 88Sr controls following in vivo CP and in vitro incubation with zymosan, calcium ionophore A23187, or phorbol ester (PMA). Intraperitoneal administration of CP resulted in the appearance of PGE2- and LTB4-releasing M phi in the spleens of control but not 89Sr mice. The incorporation and quantitative distribution of 3H-arachidonic acid into membrane lipids, however, were comparable in test and control mice. Neither zymosan nor any of the other stimulatory agents was able to effect significant release of PGE2 in vitro. No release of LTC4 by splenic M phi was detectable under experimental or control conditions. In contrast, the capacity of resident peritoneal M phi to release PGE2, LTC4, and LTB4 was apparently unaffected by 89Sr-induced bone marrow and monocyte depletion with virtually no demonstrable elicitation. Resident peritoneal M phi removed after CP in such mice showed a dramatic decrease in PGE2 release when incubated in vitro with zymosan, A23187, or PMA. These results, taken with earlier findings, demonstrate characteristically different phenotypic expression of metabolism of certain eicosanoids by splenic M phi from the spleen and the peritoneal cavity and suggest in addition that the induction of PGE2-synthesizing M phi in the spleen by CP is dependent on either an immigrant cell originating in the bone marrow or a regulatory agent derived from a bone marrow cell.
Insights
Bone marrow depletion prevents Corynebacterium parvum (CP)-induced prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) release by spleen macrophages. Peritoneal macrophages, however, maintain their eicosanoid release capabilities.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages (M phi) play a crucial role in immune responses.
- Previous studies indicated that prostaglandin-forming M phi in mouse spleens, induced by Corynebacterium parvum (CP), were absent after bone marrow depletion.
- The origin and regulation of these spleen-associated M phi remain unclear.
Purpose of the Study:
- To compare the release of prostaglandin E2 (PGE2), leukotriene C4 (LTC4), and LTB4 by splenic and resident peritoneal M phi.
- To investigate the impact of bone marrow and monocyte depletion on M phi eicosanoid synthesis.
- To elucidate the cellular origins and regulatory mechanisms of CP-induced M phi in the spleen.
Main Methods:
- CBA/J mice were treated with 89Sr to deplete bone marrow and monocytes, with 88Sr-treated mice serving as controls.
- M phi were isolated from the spleen and peritoneal cavity following in vivo CP administration.
- In vitro stimulation of M phi was performed using zymosan, calcium ionophore A23187, or phorbol ester (PMA) to assess eicosanoid release (PGE2, LTC4, LTB4).
- 3H-arachidonic acid incorporation into membrane lipids was quantified.
Main Results:
- CP administration induced PGE2- and LTB4-releasing M phi in the spleens of control mice, but not in 89Sr-treated mice.
- 3H-arachidonic acid incorporation was comparable between control and 89Sr-treated mice.
- Resident peritoneal M phi eicosanoid release (PGE2, LTC4, LTB4) was largely unaffected by 89Sr treatment, although CP-stimulated peritoneal M phi showed reduced PGE2 release in vitro.
- No LTC4 release was detected from splenic M phi under any condition.
Conclusions:
- Splenic and resident peritoneal M phi exhibit distinct phenotypic expression in eicosanoid metabolism.
- The induction of PGE2-synthesizing M phi in the spleen by CP is dependent on bone marrow-derived cells or regulatory factors.
- These findings highlight the heterogeneity of macrophage populations and their functional specialization.