Disease relevance of SAC

• METHODS: Fifty to one hundred microlitre tears were obtained from patients with active seasonal allergic conjunctivitis (SAC; n=12), vernal keratoconjunctivitis (VKC; n=18), atopic keratoconjunctivitis (AKC; n=6) and non-atopic controls (n=14) [1].
• Deoxymannojirimycin (dMM) or swainsonine (SW), which block conversion of high-mannose to complex-type N-linked glycans, strongly inhibited the production of immunoglobulin (Ig) when added to cultures of human lymphocytes together with the polyclonal B cell activators pokeweed mitogen (PWM) and Staphylococcus aureus (SAC) [2].
• Cognate phage are enriched by SAC up to 1000-fold and interacting pairs can be identified by array screening [3].
• Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation [4].
• One aliquot of CLL cells was infected with EBV, another was activated with a mixture of Staphylococcus aureus (SAC), IL-2 and the supernatant from the T-cell hybridoma MP6 (activation mixture, AcMx) and the third aliquot received both treatments [5].

High impact information on SAC

• Crosslinkage of the B cell antigen receptor by anti-mu beads or SAC results in the selective induction of hsp70 [6].
• This is in contrast to B cell differentiation signals of IL-2 alone or SAC and IL-2 in concert [7].
• The idea that both the substrate and the enzyme contribute to catalysis (substrate assisted catalysis; SAC) is applicable to guanine nucleotide-binding proteins (G proteins) [8].
• In polarized HepG2 cells an endosomal organelle, SAC, fulfills a prominent role in the biogenesis of the canalicular membrane, reflected by its ability to sort and redistribute apical and basolateral sphingolipids [9].
• Thus, for normal differentiation of human B lymphocytes into Ig secreting (plasma) cells in response to PWM and SAC, conversion of high-mannose to complex N-linked glycans is essential [2].

Chemical compound and disease context of SAC

• When retinoic acid was administered to B cells stimulated into mid to late G1 by anti-IgM antibodies (anti-mu) and Staphylococcus aureus crude cell suspension (SAC), the phosphorylation of pRB required for S-phase entry was prevented in a time- and dose-dependent manner [10].
• Cultured monocytes were stimulated with either Staphylococcus aureus (SAC) or lipopolysaccharide (LPS) [11].
• Furthermore, responses of enriched B-cell populations from HIV+ subjects and normal controls to SAC were not significantly different when assays were performed in the presence of indomethacin and exogenous lymphokines [12].
• DESIGN AND SUBJECTS: We analysed serum aldosterone (SAC) and plasma renin concentration (PRC) in 37 normotensive controls, 144 hypertensive patients with essential hypertension, and 19 patients with primary aldosteronism [13].

Biological context of SAC

• Enforced elevation of PKA activity in normal cells resulted in apoptosis by the SAC domain of Par-4 in a T155-dependent manner [14].
• Together, these observations suggest that selective apoptosis of cancer cells by the SAC domain of Par-4 involves phosphorylation of T155 by PKA [14].
• When added to B-lymphocytes stimulated with anti-immunoglobulin (anti-mu) and SAC, lovastatin (20 microM) inhibited the cells in the late G1 phase of the cell cycle [15].
• Activation of the neutrophil respiratory burst by the supernatant fraction from an alkali-treated collagen preparations (SAC) was enhanced by longer durations of exposure to alkali (1 N NaOH for 0.5-24 hr) [16].
• In a prospective study we investigated the association of kidney graft rejection with pre- and posttransplant B cell responses in vitro after stimulation with pokeweed mitogen, Staphylococcus aureus Cowan I (SAC I), or donor lymphocytes [17].

Anatomical context of SAC

• The addition of gamma-IFN together with IL 2 induced IgM and IgG secretion in SAC-stimulated B cells that was comparable with that induced by a conventional T cell factor(s) [18].
• Induction of germ-line transcripts (germ-line C gamma 1 transcript) was noted in stimulated B cells (SAC plus IL-2) at 6 h; thus, the appearance of germ-line transcripts could not be attributed to preferential growth of B cells expressing germ-line transcripts [19].
• Vesicles containing DHE traversed the cells in both directions, but vesicular export of DHE from the SAC/ARC to the plasma membrane domains was low [20].
• In this review, we will focus on the potential subcompartmentalization of the SAC in terms of regulation of membrane traffic, on how SAC relates to the endosomal system, and on how this compartment may operate in the context of other intracellular sorting organelles such as the Golgi complex, in generating and maintaining cell polarity [21].
• Next to the trans Golgi network, a subapical compartment called SAC or common endosome appears instrumental in regulating these sorting events [22].

Associations of SAC with chemical compounds

• Of various gangliosides tested, only GM2 and GM3 inhibited production of IgG subclasses and IgM, but not IgA subclasses, and thymidine uptake by human B cells stimulated with SAC plus interleukin-2 (IL-2) [23].
• N,N'-Diacetylputrescine (tetramethylenebisacetamide [TMBA]) and its six carbon analog, hexamethylenebisacetamide (HMBA), inhibited the proliferative response of human B lymphocytes to anti-mu and formalinized Cowan I strain Staphylococcal aureus (SAC) stimulation [24].
• The antiproliferative effect of these diamine derivatives was specific for anti-mu (or SAC) activation of normal B cells, because the proliferation of PHA-stimulated human T cells and transformed human B cells was not affected by the presence of TMBA or HMBA [24].
• Intracellular DHE was targeted mainly to vesicles of the subapical compartment or apical recycling compartment (SAC/ARC), where it colocalized with fluorescent transferrin and fluorescent analogs of phosphatidylcholine and sphingomyelin [20].
• An enzyme-linked immunosorbent assay was used to detect serum antibodies within Ig classes IgG, IgM, IgA, and IgE against two partially purified Trichophyton mentagrophytes-derived antigens: polysaccharide (SAC) and peptide (PEP) [25].

Physical interactions of SAC

• Fluorescent transferrin was found to be transported sequentially through basolateral SE (sorting endosomes) to a SAC/ARC (subapical compartment/apical recycling compartment) [26].

Regulatory relationships of SAC

• The addition of serum led to an increase in LPS-, SAC- and Pam3-Cys-Ala-Gly-stimulated TNF-alpha secretion, indicating that the presence of serum is critical not just for LPS stimulation [27].
• In fact, we could show that stimulation of B-cells with IL-10 somewhat suppressed SAC induced autocrine IL-6 production [28].
• Supernatants of monocytes stimulated with LPS or SAC enhanced the antiviral activity of IFN-gamma but not IFN-alpha [29].
• Staphylococcus aureus (SAC) but not lipopolysaccharide (LPS) induced IFN-alpha secretion by monocytes [29].
• IL 2 induced proliferation not only in SAC-stimulated B cells but also in an anti-mu-stimulated B cell population [18].

Other interactions of SAC

• Comparable amounts of IL-8 were induced by either LPS or Pam3-Cys-Ala-Gly, with SAC being less effective even at higher concentrations [27].
• MY4, a CD14 antibody, selectively blocked the TNF-alpha secretion induced by LPS but not by Pam3-Cys-Ala-Gly or SAC [27].
• Thus, LPS- or SAC-stimulated monocytes produced a factor(s) that augmented the biological activity of IFN-gamma [29].
• Bacterial products such as LPS or SAC have a potent IL-6 inducing effect on monocytes and minor or no effect on endothelial- and smooth muscle cells [30].
• Focusing first on regulation of germ-line (I alpha-C alpha) transcripts, we showed that C alpha 1 germ-line transcripts are induced by TGF-beta 1 alone but such induction is enhanced by Staphylococcus aureus, Cowan I (SAC) [31].

Analytical, diagnostic and therapeutic context of SAC

• Cortical actin assembly played a role in regulating the activity of stretch-activated, calcium-permeable channels (SAC) since sustained force application desensitized SAC to subsequent force applications, and the decrease in stretch sensitivity was reversed after treatment with cytochalasin D [32].
• PWM was used for T cell-dependent B cell stimulation in an allogeneic coculture system, and SAC I for T cell- and monocyte-independent B cell stimulation [33].
• The concentrate obtained from ultrafiltration (greater than 30,000 molecular weight) of SAC (1 N NaOH for 24 hr) retained the stimulatory factor [16].
• RESULTS: Eight patients (four in the SAC group and four in LAC group) could not continue therapy because of severe diarrhoea, and three did not take the 13C urea breath test after therapy [34].
• From its behavior in pulsed field gel electrophoresis, FISH analysis of stretched DNA fibers, and its appearance under scanning confocal microscopy, it was concluded that the SAC is a circularized and multimerized derivative of the original YAC [35].

References