Joachim Langstein

A soluble form of CD137 (ILA/4-1BB), a member of the TNF receptor family, is released by activated lymphocytes and is detectable in sera of patients with rheumatoid arthritis

CD137 (ILA/4‐1BB) is a member of the tumor necrosis factor receptor family and regulates activation, proliferation and programmed cell death in T lymphocytes. Here we show the existence of a soluble form of CD137 (sCD137) of 16 kDa. sCD137 is released by activated lymphocytes, and in contrast to membrane‐bound CD137, expression of sCD137 seems to be restricted to lymphocytes. sCD137 is generated by alternative splicing and two splice variants were identified. sCD137 is present at low levels in sera of some healthy donors (5/12; mean = 0.18 ng/ml) and is significantly enhanced in sera of patients with rheumatoid arthritis (12/12; mean = 3.58 ng/ml).

CD137 is expressed on blood vessel walls at sites of inflammation and enhances monocyte migratory activity

The cytokine receptor CD137 is a member of the TNF receptor family and a potent T cell costimulatory molecule. Its ligand is expressed on antigen presenting cells as a transmembrane protein and it too can deliver signals into the cells it is expressed on (reverse signaling). In monocytes, immobilized CD137 protein induces activation, prolongation of survival and proliferation. Here we show that recombinant immobilized CD137 protein enhances migration of monocytes in vitro. Further, CD137 expression on spheroids leads to a significantly enhanced infiltration by monocytes. The migration‐inducing activity of CD137 could be confirmed in vivo. Matrigel, which was coated with recombinant CD137 protein and was inserted into the flanks of mice attracted large numbers of monocytes and was heavily infiltrated by these cells. In vivo, expression of CD137 by blood vessel walls at sites of inflammation was detectable by immunohistochemistry. CD137 expression is inducible by proinflammatory cytokines in endothelial cells, suggesting that a physiological function of CD137 may be the facilitation of monocyte extravasation in inflammatory tissues.—Drenkard D., Becke F. M., Langstein J., Spruss T., Kunz‐Schughart L.A., Tan T.E., Lim Y.C., Schwarz H. CD137 is expressed on blood vessel walls at sites of inflammation and enhances monocyte migratory activity. FASEB J. 21, 456–463 (2007)

Identification of CD137 as a potent monocyte survival factor

CD137 (ILA/4‐1BB), a member of the tumor necrosis factor (TNF) receptor family, promotes adherence and prolongs survival of human peripheral monocytes. It induces a strong expression of macrophage colony‐stimulating factor (M‐CSF), an essential monocyte survival factor. Monocyte survival induced by CD137 is primarily mediated by M‐CSF and to a lesser extent by granulocyte‐macrophage colony‐stimulating factor and IL‐3. Survival and induction of M‐CSF are mediated via reverse signaling through a CD137 ligand expressed constitutively by peripheral monocytes. J. Leukoc. Biol. 65: 829–833; 1999.

CD137‐induced apoptosis is independent of CD95

CD95 (APO‐1/Fas) and CD137 (ILA/4‐1BB) are members of the tumour necrosis factor receptor family, and both are involved in induction of apoptosis in lymphocytes. Contrary to the case of CD95, apoptosis by CD137 is caused by cross‐linking of the respective ligand rather than the receptor. Nothing is known so far about the mechanism of CD137‐induced cell death. Here, we show that immobilized CD137 protein induces expression of CD95 in resting primary T and B lymphocytes. However, induction of apoptosis by CD137 is independent of CD95, because: (1) antagonistic anti‐CD95 antibody fragments do not block CD137‐induced apoptosis; and (2) CD137, but not anti‐CD95, can induce apoptosis in resting lymphocytes.

Cis-9,10-octadecenoamide, an endogenous sleep-inducing CNS compound, inhibits lymphocyte proliferation

This study examined the immunoregulatory effects of cis-9,10-octadecenoamide (CODA), a recently identified endogenous sleep-inducing brain lipid. CODA displays structural and functional similarities to anandamide, the endogenous ligand for the cannabinoid receptors. CODA proved to be immunosuppressive. It inhibited proliferation of anti-CD3- and ConA-activated primary lymphocytes and proliferation of T- and B-cell lines. Complete inhibition occurred at concentrations of 100 microM. This effect was stereospecific, since the trans-stereo isomer of CODA did not inhibit proliferation at identical concentrations. A further control compound, octadecanamide, identical to cis-9,10-octadecenoamide, besides lacking the 9,10 carbon double bond, also did not affect proliferation. The antiproliferative effects of CODA occurred rapidly, since 24-h exposure to CODA was sufficient for complete inhibition of proliferation. CODA and anandamide worked synergistically in inhibiting lymphocyte proliferation. No significant effects of CODA on monocyte functions, as assessed by LPS-induced TNF alpha secretion, could be detected.

Recovery of functional, recombinant baculovirus-produced proteins from insoluble precipitates in insect cells

▼The baculovirus protein expression system enjoys widepopularity due to high yields and eukaryotic post-translational modification of expressed proteins (Ref. 1).Commercial manufacturers also advertise easy purifica-tion of recombinant proteins, especially when expressedas fusion proteins with glutathione-